Uveitis accounts for about 10% of visual impairment in the United States. There is reasonable evidence to suggest that autoimmunity is a contributing factor in the initiation and perpetuation of some of these ocular inflammatory diseases. Investigation into such an immunologic etiology has necessitated the development of animal models. A thorough description of the immune response in animal models is vital to relating animal studies to human uveitis, so that specific preventive, diagnostic and therapeutic protocols can be devised. The overall objective of this laboratory is to define the role of specific autoantigens and immune mechanisms in experimental uveitides. Recent laboratory and clinical studies would suggest that retinal Muller cells play a role in uveitis. They may be nonspecific responders to ocular assault, immunomodulators in the eye, or targets of autoimmune attack. Various combinations and permutations of these activities may participate to produce different clinical manifestations of uveitis. We plan a series of experiments to examine each of these possible functions. Changes in immunoreactivity of retina and pineal gland will be monitored in animals with different forms of experimental uveitis. Specific molecules monitored will include: glial fibrillary acidic protein, S-100 protein, MHC class II antigens, retinal S-antigen, and synthetic peptide-M of S-antigen. Changes will be compared in experimental autoimmune uveoretinitis induced by retinal S-antigen, strictly posterior uveitis of U-antigen, and strictly anterior uveitis of endotoxin. Animals will be routinely monitored for clinical, histopathologic, and immunologic manifestations of autoimmune uveitis. Modulation of ocular responses in relation to systemic responses to different autoantigens will give a clearer understanding of Muller cell activity in these models. Ocular inflammation to synthetic peptides can be enhanced by injecting more than one peptide at a time or by the addition of endotoxin or pertussis adjuvant. Ocular inflammation can be reduced by oral presentation of antigen or peptides prior to sensitization or by blocking of the inciting molecule with monoclonal antibodies to specific epitopes. Further insight to Muller cell participation can be gained by studying S- antigen and U-antigen induced uveitis following alteration of Muller cells by prior sensitization to peptide M.